Organic esters of 2-(2-diethylaminoethoxy)-ethanol and their process of preparation



ORGANIC ESTERS F -mmmrmo- ETHOXY)-ETHANOL AND THEIR PROCESS OF PREPARATION 1 a.

Henri Morren, Forest-Brussels, Belgium, assignor to Union Chimique Belge, Societe Anonyme, Brussels, Belgium, a Belgian company No Drawing. Application March 23, 1954 Serial No. 418,238

Claims priority, application Belgium June 26, 1953 5 Claims. (Cl. 260469) This invention relates to organic esters of Z-(Z-diethylam1uo-ethoxy)-ethanol v I have found that certain of these esters and their hydrochlorides and acid citrates possess considerable spasmolytic power.

I have found that whilst the desired esters may be prepared by the methods commonly employed for esterification, it is preferable to esterify the said amino alcohol with a carbonyl halogenide of the selected organic acid, with or without the use of a hydrogen chloride acceptor, or to make the trans-esterification of the methyl or ethyl ester of the selected organic acid by means of the said amino alcohol with liberation of methanol or ethanol respectively.

The esters and their hydrochlorides or acid citrates according to my invention, and their preparation, are described in the following examples.

EXAMPLE 1 Z-(Z-diethylamino-ethoxy -ethyl ester of 1 -phenyl-1 -cyclopentanecarboxylic acid and its hydrochloride A mixture of 0.5 mol of l-phenyl-l-cyclopentanecarbonyl chloride and of 0.5 mol of Z-(Z-diethylaminoethoxy)'-ethanol in 300 mls. of toluene is heated under reflux for 20 hours. The mixture is thereafter made alkaline by means of an aqueous solution of caustic soda and decanted; the toluenic layer is washed with water and concentrated in vacuo. The residue is distilled under high vacuum. After two fractional distillations there is obtained, in 85 percent yield, the desired ester in the form of its base. Boiling point 164 C./ 0.1 mm. Hg.

The corresponding hydrochloride is prepared by dissolving the base in ether and by treating it with an ethereal solution of hydrochloric acid. The salt may be recrystallized by dissolving it in very little alcohol or acetone followed by the addition of ether. Melting point 7l72 C.

EXAMPLE 2 2-(Z-diethylamirzo-ethoxy)-ethyl ester of 1 -phenyl-1 -cyclohexanecarboxylic acid and its hydrochloride 0.35-0-0 0 0 CHiCHLO OH2CH2N(C2H5)Z.HC1

CH2 CH2 This ester is obtained as in Example 1 by reacting 1- phenyl-l-cyclohexanecarbonyl chloride and the' amino alcohol.

Boiling point of the ester 173 C./0.1 mm. Hg. The hydrochloride is prepared in ether.

2 EXAMPLE 3 2-(2-diethylamino-ethoxy)-ethyl ester of 4-phenyl-4-tetrahydropyranecarboxylic acid and its acid citrate OlHs-CC 0 0 01120112. 0 OHiC H2N(CIH5)Z.1 molecule citric acid (EH1 CH2 C Ha Hz The ester is prepared. as in "Example 1 by means of 4-phenyl-4-tetrahydropyranecarbonyl chloride and the amino alcohol. Boiling point of the ester 170 C./ 0.02 mm. Hg. The acid citrate is prepared in ether.

. EXAMPLE 4 2-(2-diethylamino-ethoxy)-ethyl ester of 1 -phenyl-1 -cy cl0- propanecarboxylic acid and its acid citrate OQHEOC 0 0 cHiCHio Cfi2CH2N C2HQL1 molecule citric acid According to Example 1,l-pheuyl-l-cyclopropanecarbonyl chloride and the amino alcohol are allowed to react. Boiling point of the ester 145 C./0.02 mm. Hg. The acid citrate, prepared in ethereal medium, is hygroscopic.

EXAMPLE 5 I Z-(Z-diethylamino-ethoxy)-ethyl ester of diphenylacetic acid and its acid citrate CuHa CH-C 0 QH OHLO 0HlOH2N(C2H5)2-l molecule of citric acid and the extract is washed with water.

The reaction of the diphenylacetyl chloride and of the amino alcohol is carried out as in Example 1. point of the ester 175 C./ 0.02 mm. Hg. The acid citrate, prepared in an ethereal medium (1 mol of ester and 1 mol of citric acid), is hygroscopic.

EXAMPLE 5 2 (2. diethylamino-ethoxy)-ethyl, ester of phenylcyclohexylacetic acid and its acid citrate CaHi C H-C O O CHaC 112.0 CH2CH2N( C2H5)z.1 molecule citric acid EXAMPLE 7 2 (2 diethylamino ethoxy) ethyl ester of phenyl-(Z- thenyl)-acetic acid and its acid citrate CaHs OIL-C O 0 0112.0 CH2CH2N(C2H5).1 molecule citric acid U011:

A mixture of 0.1 mol phenyl-(Z-thenyl) -acetyl chloride (boiling point -160 C./0.5 mm. Hg) and of 0.1 mol of the amino alcohol in 100 mls. of pyridine is heated with reflux for one hour. The mixture is shaken in 1 litre of water and extracted twice by means of benzene After evaporation of the solvent, the residue is distilled under high vacuum. The ester is obtained in a 75 percent yield. Boiling point of the ester -180 C./0.0l mm. Hg.

The acid citrate is prepared in ether from equimolar quantities of the ester and citric acid.

Boiling 3 EXAMPLE 8 2-(Z-diethylamino-ethoxy)-ethyl ester of phenyl-(Z-furfuryl)-acetic acid onooocnlornocmommczmn H nix-n 0.3 gram of metallic sodium are dissolved in 12 grams of 2-(2-diethylamino-ethoxy)rethanol and there are added thereto 9 grams of methyl phenyI-(Z-furfuryl) -acetate (boilingpoint' 1171l8 C./0.05 mm..Hg). The methanol formed and the excess of amino. alcohol are distilled oh. The residue is taken up by means of benzene and washed with water. After-evaporation of the solvent, the. product obtained by transesterification is distilled at high vacuum. There are obtained 7.9 grams of the ester (boiling point 150 C./0.0l mm. Hg).

The methyl phenyl-(Z-furfuryl)-acetate is obtained by the action of 2-furfuryl chloride on the sodium salt of phenyl-acetonitrile, followed by the saponification of the phenyl-(Z-furfuryl)-acetonitrile (boiling. point 167-170" C./-1 3 mm. Hg) and the esterification of the .carboxyl r p- The phenyl-(2-furfuryl) -acetic acid (melting point 101 C.) is methylated in anethereal medium by the addition of an excess of diazomethane.

EXAMPLE9' 2-(Z-diethylamino-ethoxy)-ethyl ester of 1-(alphacycloh exyl-pmethoxybenzyl) 4 piperazinecarboxylic acid and its dihydrochloride 4 hexyl-p-methoxybenzyl chloride (melting point 98 C.) obtained from the corresponding alcohol. After cooling, the mass is taken up with water, rendered alkaline by means of caustic soda and extracted with benzene. The benzene solution is washed with; water and concentrated and the residue distilled in vacuo.

I claim:

1. A compound selected from the group consisting of an ester having the formula (C2H5 2 wherein R is a radical selected from the group consisting 3. A process for'producing an ester having the formula RCO 0CH CH QCH CH N(C H wherein R is a radical selected from. the group consisting This ester is prepared according to the method given in Example 8 by the transesterification of the corresponding ethyl carboxylate by means of. amino alcohol in. excess, in the presence of metallic sodium. Boiling point of the ester 260 C./ 0.005 mm. Hg (with slight decomposition).

The dihydrochloride is obtained by dissolving the ester in acetone and by saturating the solution with gaseous hydrochloric acid. The salt is thereafter precipitated by the addition of-ether.

- The ethyl-'1-(alpha-cycloheXyl-p.methoxybenzyl)-4piperazinecarboxylate (boiling point 205 C./ 0.05 mm. Hg) is prepared in 70 percent yield by the reaction of 0.2 mol of monocarbethoxypiperazine with 0.1 mol of alpha-cyclowhich comprises esterifying- 2'-(Z-diethylamino-ethoxy)- ethanol with. a derivative of a carboxylic acid having the formula RCOOH, said derivative being selected from References Cited in the file of this patent UNITED STATES PATENTS 2,512,307 Clintonet a1 June 20, 1950 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF AN ESTER HAVING THE FORMULA 